CME Author: Vicki Brower
Study Authors: Virginia J. Howard, Tracy E. Madsen, et al.
Target Audience and Goal Statement:
Internists, family medicine specialists, neurologists
The goal is to better understand sex and age differences in stroke risk between African-American and white individuals.
Questions Addressed by this Study:
- What are the incidence and risk factors for ischemic strokes among African-American and white individuals?
- Are there race-sex differences in the associated risk factors?
Study Synopsis and Perspective
In the U.S., it is known that the largest racial disparity in stroke risk is between African-American and white individuals. From ages 45 to 64, African-American individuals have a threefold higher risk of stroke than white individuals, but these differences fade by age 85. However, there is a dearth of studies that describe sex differences in stroke risk in African-American and white individuals.
This new national cohort study found that African-American women in their late 60s and early 70s had the same stroke risk as African-American men, unlike patterns found among white men and women. From ages 45 to 74, white women were less likely than white men to have an ischemic stroke, but African-American women had a lower stroke risk than African-American men only until age 64, reported Virginia Howard, PhD, of the University of Alabama at Birmingham, and colleagues in JAMA Neurology.
Specifically, among white and African-American adults in the U.S., women of both races had a lower stroke risk from ages 45 to 64, but there was a similar risk of stroke for men and women ages 75 and older for both races. For individuals age 65 to 74 years of age, however, researchers found that white women were at lower stroke risk than their male counterparts. Thus, African-American women seemed, in this study, to lose their protection from stroke at a younger age than white women. Also, in whites there were differences by sex in the association of diabetes, blood pressure, antihypertensive use, and heart disease on stroke risk, whereas a differential association of risk factors by sex was not observed in African-American individuals. Authors warned that this should be interpreted with caution because the sex-race interaction test did not reach statistical significance.
For their study, Howard and colleagues studied 25,789 participants ages ≥45 from the national REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort. Stroke-free participants enrolled from 2003 through 2007, and were followed until October 2016; 54.9% were female and 39.9% were African-American. African-American individuals and residents of the southeastern U.S. were over-sampled in this study.
Compared with white individuals, African-American individuals of both sexes had lower socioeconomic status and a generally worse risk factor profile than white individuals — they had higher systolic blood pressure levels and were more likely to be taking anti-hypertensive medications. The prevalence of diabetes was approximately twice as high for African-American participants as white participants.
Over the follow-up period, 939 ischemic strokes occurred: 159 in African-American men, 326 in white men, 217 in African-American women, and 237 in white women. Crude stroke incident rates showed:
- From ages 45 to 64, white women had 32% lower stroke risk than white men (IRR 0.68, 95% CI 0.49-0.94), and African-American women had a 28% lower risk than African-American men (IRR 0.72, 95% CI 0.52-0.99).
- From ages 65 to 74, lower stroke risk in women vs men persisted in white individuals (IRR 0.71, 95% CI 0.55-0.94), but not in African-American individuals (IRR, 0.94, 95% CI 0.68-1.30); the race-sex interaction was not significant.
- At ages ≥75, there was no sex difference in stroke risk for either race.
In a fully adjusted model, a differential association of risk factors by sex on the risk of stroke was not seen in African-American individuals. But among white participants, diabetes, higher systolic blood pressure, and a history of heart disease increased stroke risk more for women than men, while using anti-hypertensive medications was tied to a lower stroke risk for women.
JAMA Neurology, Dec. 10, 2018; doi: 10.1001/jamaneurol.2018.3862
Study Highlights: Explanation of Findings
Sex differences in the association of stroke risk factors with incident stroke have been studied, but results have not been consistent across studies in different settings, researchers wrote, and added that they are unaware of other studies that examined sex-specific differences by race and by age. Therefore, Howard and colleagues designed their new study in order to focus on sex-specific differences according to race — to assess whether African-American individuals shared the same pattern as white individuals, of a higher men-to-women relative risk of stroke between ages 45 and 64, a smaller ratio between ages 65 and 74, and little differences in ages greater than 75, and to assess the dual effect of sex and race on the magnitude of the association of risk factors with the risk of ischemic stroke.
“It was already known that women have a greater protection from stroke at younger ages, but women have relatively similar stroke risk as men at the oldest ages,” said Howard. “What was not known was whether this age pattern of stroke risk was the same for blacks and whites,” she said.
“Our work suggests that the men-to-women stroke risk may be different by race for the age group 65 to 74 years: for blacks in this age group, the lower stroke risk in women compared to men was not evident, while it remained lower in whites,” Howard told MedPage Today.
“For individuals between 65 and 74, there is a suggestion that sex differences may only be present in whites: white women ages 65 to 74 years have fewer strokes than do white men in that age group, but among African-American participants aged 65 to 74, stroke races are similar in men and women. The investigators did not actually find evidence of a significant interaction by sex and race, so we have to be cautious in the interpretation of the results,” observed Rebecca Gottesman, MD, PhD, of Johns Hopkins University in Baltimore, who was not involved with the study.
Although the researchers adjusted for many factors by which the four race-sex groups differ, “they are so different in many ways that it’s likely there are continued other ways in which these groups differ,” Gottesman told MedPage Today. “Therefore, it is hard to know for sure if this suggestion of a difference in sex disparities among blacks between 65 and 74 years old is truly due to a different pattern by race or is simply driven by differences in underlying risk factors.”
“From the actual stroke event numbers, it looks as though the relative lack of difference in stroke rates between black men and women between 65- and 74-years-old is driven by increased rates of stroke in black women, rather than lower rates in black men,” she added. “Stroke prevention strategies should consider the increased risk in some of these groups,” Gottesman said.
In their analysis of the REGARDS study, Howard and colleagues found significant interactions with sex for whites but not African-Americans. For whites, the finding is “complex” because they saw a larger association of blood pressure with stroke risk in women than men, but a smaller association with the use of antihypertensive treatment. “
In conclusion, researchers wrote, sex-specific risk factor management to prevent stroke may be needed for white individuals but not for African-American individuals “because there was no evidence of a sex difference in the role of risk factors in black individuals. There appears, then, a “mixed message” in which blood pressure seems more important for women than men, but antihypertensive use seems more important for men than women. In African-Americans there was no evidence of a significant difference by sex in the association of systolic blood pressure or use of antihypertensive medications.
Strengths of the study include the large number of both racial groups, men and women, across age groups and across the U.S., and the large number of ischemic stroke events considered. This combination meant that sex-associated, race/ethnicity associated, and age-associated differences in stroke incidence and differences in the association with stroke risk factors could be studied.
There were some limitations to the study. Participants may not be representative of the general population, and some data may have been misclassified. The study was observational and causal inferences cannot be made. Not all medical records for suspected stroke could be obtained, researchers said, but multiple imputation methods helped address this.
Judy George wrote the original story for MedPage Today